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Biomedical subjects

F Wong

Publications and source records attributed to F Wong.

At least 109 records · Page 6Linked to original sources
PubMed1998

New combination of the old drugs for elderly patients with small-cell lung cancer: a phase II study of the PAVE regimen.

PURPOSE: A regimen of cisplatin, doxorubicin, vincristine, and etoposide (PAVE) was designed for patients with small-cell lung cancer (SCLC) who were older than 65 years, with the following objectives compared with standard chemotherapy regimens: maintain efficacy, diminish toxicity, enhance compliance, and improve chemotherapy administration convenience at an acceptable cost. PATIENTS AND METHODS: The PAVE regimen consisted of cisplatin 30 mg/m2 intravenously (i.v.) day 1; doxorubicin 40 mg/m2 i.v. day 1; vincristine 1.0 mg/m2 i.v. day 1; and etoposide 100 mg/m2 i.v. day 1 and orally days 3 and 5. Cycles were repeated every 3 weeks for four cycles. Patients with limited-stage disease and selected patients with extensive-stage disease received thoracic irradiation delivered concurrently with etoposide-cisplatin (EP) at the time of the second chemotherapy cycle. RESULTS: Sixty-six eligible patients were treated, which included 25 patients with limited-stage disease and 41 patients with extensive-stage disease. Median survival was 70 weeks and 5-year survival was 25% for limited-stage disease. Median survival was 46 weeks for extensive-stage disease. Only one treatment-related death occurred and severe toxicity was infrequent. The median delivered dose-intensity was according to protocol and the mean delivered total dose was 80% of intended. CONCLUSION: The treatment outcome achieved with PAVE in a phase II study of elderly patients compared favorably with published results of standard regimens in patient populations with better prognostic factors. Because the PAVE regimen can be delivered with good compliance, has acceptable toxicity, and is associated with logistic advantages compared with standard regimens, this protocol is suitable for further investigative trials in elderly patients with SCLC.

Age Factors↗
PubMed1998

Rhodopsin transgenic pigs as a model for human retinitis pigmentosa.

PURPOSE: To further characterize the retinas of Pro3471Leu rhodopsin transgenic pigs, a model for human retinitis pigmentosa. METHODS: Retinas from normal and transgenic pigs, newborn to 20 months old, were processed for light and electron microscopic immunocytochemical examination. RESULTS: At birth, rod numbers were normal in the transgenic retinas, but their outer segments were short and disorganized and their inner segments contained stacks of rhodopsin-positive membranes. The newborn rod synapses lacked synaptic vesicles and ribbons and had numerous rhodopsin-positive, filopodia-like processes that extended past the cone synapses into the outer plexiform layer. Rod cell death was apparent by 2 weeks and was pronounced in the mid periphery and central regions by 6 weeks. Far peripheral rods were initially better preserved, but by 9 months virtually all rods had degenerated. Cones degenerated more slowly than rods, but by 4 weeks the cone synapses were shrunken and some mid peripheral cones had lost their immunoreactivity for phosphodiesterase-gamma, arrestin, and recoverin. From 9 months to 20 months, the cone outer segments shortened progressively, and more cones lost immunoreactivity for these proteins. CONCLUSIONS: The rhodopsin transgenic pig retina shares many cytologic features with human retinas with retinitis pigmentosa and provides an opportunity to examine the earliest stages in photoreceptor degeneration, about which little is known in humans. The finding of abnormal rhodopsin localization in newborn rods is consistent with misrouting of mutant rhodopsin as an early process leading to rod cell death. Novel changes in the photoreceptor synapses may correlate with early electrophysiological abnormalities in these retinas.

Animals↗
PubMed1998

Pathophysiology and treatment of hepatorenal syndrome.

Hepatorenal syndrome is a progressive oliguric renal failure complicating the course of advanced cirrhosis and ascites. Significant hemodynamic changes occur in these patients consisting of marked systemic arterial vasodilatation and renal vasoconstriction. Traditionally, the systemic arterial vasodilatation with the consequent underfilling of the effective arterial blood volume has been held responsible for the pathogenesis of the renal vasoconstriction. Recent data showing a dissociation between the extent of arterial underfilling and the development of renal dysfunction in these patients have lead to the proposal of a hepatorenal interaction directly causing the renal vasoconstriction, with arterial underfilling secondarily contributing further to the renal vasoconstriction. Diagnosis of hepatorenal syndrome remains one of exclusion. Treatment is largely ineffective except for liver transplantation, which unfortunately is not available to all patients because of their short survival. Prognosis is very poor once it has developed. Therefore, physicians should be alert to avoid precipitating factors in these patients. Recent development of new therapies such as the use of a transjugular intrahepatic portosystemic shunt or systemic vasoconstrictors appear promising, but their efficacy should be evaluated in prospective randomized controlled trials.

Disease Management↗
PubMed1997

Correlation of DNA fragmentation and chromatin condensation in apoptotic nuclei of the Ser 6 mouse retina.

The form of cell death known as apoptosis was first described in thymocytes. The hallmarks of apoptosis include chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA fragmentation. DNA fragmentation can be visualized morphologically by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method that labels the cut DNA ends. However, at the light microscopic (LM) level, TUNEL-positive nuclei cannot readily be correlated with the other hallmarks of apoptosis. In the retina, chromatin condensation and DNA fragmentation are the major features of developmental cell death as well as photoreceptor degeneration. We performed TUNEL at the electron microscopic (EM) level, which permitted correlation of DNA fragmentation with chromatin condensation. We studied the retinas of transgenic mice (Ser 6) expressing the Pro347Ser mutant rhodopsin gene during developmental cell death (age 7 days) and photoreceptor degeneration (age 21 days). We found that 90% of the nuclei showing chromatin condensation were TUNEL positive as well. Our results demonstrated DNA fragmentation and chromatin condensation in the same cells as they underwent apoptosis in vivo, confirming the notion that these processes are concomitant events, and by implication, that activation of an endogenous endonuclease is an important step in the death process of retinal neurons.

Animals↗
PubMed1997

The percutaneous absorption of topically applied tretinoin and its effect on endogenous concentrations of tretinoin and its metabolites after single doses or long-term use.

BACKGROUND: The percutaneous absorption of topically applied tretinoin cream and emollient cream formulations has not been comprehensively studied. OBJECTIVE: To assess tretinoin absorption and plasma levels of tretinoin and its metabolites after single and repeated topical tretinoin doses. METHODS: In study 1, 28 subjects were equally divided into four treatment groups that received a single dose of tritiated tretinoin in a 0.05% formulation of emollient cream (Renova, Retinova) or cream (Retin-A) alone or after 28 days of repeated nonradioactive doses. In study 2, subjects received single topical doses of tritiated tretinoin cream alone (n = 5) or after 1 year of nonradioactive applications (n = 4). Plasma, urine, and fecal samples were analyzed to determine absorption; plasma samples in study 1 were also analyzed for concentrations of tretinoin and its metabolites. RESULTS: Percutaneous absorption of tretinoin was approximately 2% after a single dose and after 28 days of daily application. In patients receiving long-term therapy (i.e., > 1 year), absorption averaged 1.1%. Mean plasma concentrations of tretinoin after 28 days of treatment with either tretinoin emollient cream or tretinoin cream were not significantly changed when compared with the corresponding endogenous concentrations before treatment. CONCLUSION: Minimal percutaneous absorption of tretinoin was obtained after its topical application in cream formulations. Neither single-dose nor long-term treatment with topical tretinoin formulations appeared to affect the endogenous levels of tretinoin or its metabolites.

Administration, Topical↗
PubMed1997

Postradiation osteonecrosis of the mandible: a long-term follow-up study.

OBJECTIVES: The objective of this study was to assess the long-term progress of 26 patients who experienced postradiation osteonecrosis of the jaw between 1975 and 1989. STUDY DESIGN: Of 26 patients who had been previously managed with hyperbaric oxygen therapy as a part of their treatment for postradiation osteonecrosis of the jaw, 20 were evaluated to determine their current status of the condition: resolved, chronic persisting (unresolved), or active progressive (symptomatic). RESULTS: Two of 20 patients experienced recurrences of the condition. In one of these patients, surgical treatment was identified as the stimulus of postradiation osteonecrosis. In the other patient, the recurrence appeared to be related to periodontal disease activity. In 60% (12 of 20) of the patients, the condition remained resolved, improvement in clinical staging occurred in 10% (2 of 20) (from symptomatic to unresolved or resolved), and 20% (5 of 20) of the patients continued to demonstrate chronic persisting postradiation osteonecrosis at the end of the long-term follow-up period. CONCLUSION: This study supports the contention that postradiation osteonecrosis can occur at any time after radiation therapy, and that patients remain at risk up to 231 months after treatment of the cancer and probably indefinitely after radiation therapy. Our findings also suggest that risk of second episodes of the condition after management of an initial episode is low. In addition, our follow-up study revealed that chronic nonprogressive postradiation osteonecrosis can remain stable without extensive intervention including combined hyperbaric oxygen therapy and surgery.

Adult↗
PubMed1997

Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa.

Patients with retinitis pigmentosa (RP) typically develop night blindness early in life due to loss of rod photoreceptors. The remaining cone photoreceptors are the mainstay of their vision; however, over years or decades, these cones slowly degenerate, leading to blindness. We created transgenic pigs that express a mutated rhodopsin gene (Pro347Leu). Like RP patients with the same mutation, these pigs have early and severe rod loss; initially their cones are relatively spared, but these surviving cones slowly degenerate. By age 20 months, there is only a single layer of morphologically abnormal cones and the cone electroretinogram is markedly reduced. Given the strong similarities in phenotype to that of RP patients, these transgenic pigs will provide a large animal model for study of the protracted phase of cone degeneration found in RP and for preclinical treatment trials.

Animals↗
PubMed1997

The mechanism of the initial natriuresis after transjugular intrahepatic portosystemic shunt.

BACKGROUND & AIMS: The pathogenesis of the delayed natriuresis after transjugular intrahepatic portosystemic shunt (TIPS) insertion is unknown. This was studied to elucidate the mechanism involved. METHODS: In 12 patients with cirrhosis and refractory ascites after TIPS, systemic and renal hemodynamics, renal sodium handling, central blood volume, neurohumoral factors, and hepatic function were studied weekly after the shunt with the patients receiving a diet of 20 mmol sodium/day. RESULTS: Two weeks after TIPS, the initial natriuresis (4 +/- 1 to 18 +/- 3 mmol/day; P < 0.05) was associated with significant reductions in corrected sinusoidal pressure (24.4 +/- 1.8 to 7.5 +/- 0.4 mm Hg; P < 0.001), proximal renal tubular reabsorption of sodium (P = 0.05), and renin-angiotensin-aldosterone activity (P < 0.05), but with significant systemic vasodilatation (P < 0.05). At 4 weeks, negative sodium balance was achieved (52 +/- 21 mmol/day; P < 0.01), despite continued systemic arterial vasodilatation, associated with significant increases in total central and cardiac volumes (P < 0.05) and normalization of serum aldosterone levels (P < 0.01). Four late responders were significantly older (P = 0.01) and had significantly lower baseline glomerular filtration rates (P = 0.02). CONCLUSIONS: In cirrhosis, sinusoidal portal hypertension and an activated renin-angiotensin-aldosterone system seem to be important in the pathogenesis of sodium retention. Systemic vasodilatation without arterial underfilling does not prevent natriuresis. Delayed natriuresis after TIPS is associated with increasing age and pre-TIPS renal impairment.

Adult↗
PubMed1997

Review: the controversy over the pathophysiology of ascites formation in cirrhosis.

The pathogenesis of renal sodium retention and ascites formation in cirrhosis is a subject of much controversy. The generally accepted 'peripheral arterial vasodilatation hypothesis' seems to best explain the mechanism of sodium retention and other clinical findings, such as the hyperdynamic circulation of cirrhosis. However, recent data in pre-ascites and in early ascites do not seem to conform to the peripheral arterial vasodilatation hypothesis. Sodium handling abnormalities can be demonstrated in pre-ascitic cirrhosis when patients are challenged with a sodium load, in the absence of systemic vasodilatation or arterial underfilling. Therefore, an alternative hypothesis with a direct hepatorenal interaction, acting via sinusoidal portal hypertension and/or hepatic dysfunction as the affector mechanism, is proposed to be the initiating event in renal sodium retention in cirrhosis. The second and later process is the development of systemic arterial vasodilatation, possibly due to the presence of excess systemic vasodilators and/or decreased responsiveness of the vasculature to endogenous vasoconstrictors. This, in turn, will lead to a relatively underfilled circulation with consequent activation of neurohumoral systems, promoting further renal sodium retention as described by the peripheral arterial vasodilatation hypothesis and ultimately leading to ascites. When compensatory natriuretic mechanisms fail, refractory ascites develops and hepatorenal syndrome sets in. Thus, renal sodium retention in cirrhosis is the result of interplay of many factors, with direct hepatorenal interaction predominating in earlier stages of the cirrhotic process, while systemic vasodilatation becomes a more important pathogenetic factor as the disease progresses.

Ascites↗
PubMed1997

Pharmacokinetic profile of levofloxacin following once-daily 500-milligram oral or intravenous doses.

The pharmacokinetics of once-daily oral levofloxacin (study A) or intravenous levofloxacin (study B) in 40 healthy male volunteers were investigated in two separate randomized, double-blind, parallel-design, placebo-controlled studies. Levofloxacin at 500 mg or placebo was administered orally or intravenously as a single dose on day 1; daily oral or intravenous dosing resumed on days 4 to 10. In a third study (study C), the comparability of the bioavailabilities of two oral and one intravenous levofloxacin formulations were investigated with 24 healthy male subjects in an open-label, randomized, three-way crossover study. Levofloxacin at 500 mg as a single tablet or an intravenous infusion was administered on day 1; following a 1-week washout period, subjects received the second regimen (i.e., the other oral formulation or the intravenous infusion); the third and final regimen was administered following a 1-week washout period. The concentrations of drug in plasma and urine were measured by validated high-pressure liquid chromatography methods. Pharmacokinetic parameters were estimated by noncompartmental methods. In both study A (oral levofloxacin) and study B (intravenous levofloxacin), steady state was attained within 48 h after the start of the multiple dosing on day 4. Levofloxacin pharmacokinetics were linear and predictable for the single and multiple 500-mg, once-daily oral and intravenous dosing regimens, and the values of the pharmacokinetic parameters for the oral and intravenous administrations were similar. Study C indicated that levofloxacin was rapidly and completely absorbed from the oral tablets, with mean times to the maximum concentration of drug in serum of approximately 1.5 h and mean absolute bioavailability of > or =99%. These results support the interchangeability of the oral and intravenous routes of levofloxacin administration.

Administration, Oral↗
PubMed1997

Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites.

OBJECTIVE: Large volume paracentesis is an effective treatment for refractory ascites, but the need for routine infusion of albumin or other volume expanders remains controversial. The aim of this study was to assess the short term effects of a single 5-L paracentesis without albumin replacement on total central blood volume, systemic and renal hemodynamics, sodium homeostasis, and neurohumoral factors. PATIENTS AND METHODS: Twelve patients with biopsy-proven cirrhosis and tense, diuretic-resistant ascites were studied before and 48 h after a single 5-L paracentesis without albumin infusion. Systemic hemodynamics and total central blood volume were assessed using radionuclide angiography. Glomerular filtration rate and effective renal plasma flow were measured by inulin and para-aminohippurate clearances, respectively. Lithium clearance was used as an index of proximal tubular reabsorption of sodium. In addition, plasma concentrations of neurohumoral factors were determined. RESULTS: Total central blood volume was 2.41 +/- 0.33 L/m2 (mean +/- SEM) before and 2.34 +/- 0.18 L/m2 48 h after large volume paracentesis (p = 0.76). Similarly, no differences were detected in the cardiac index, glomerular filtration rate, effective renal plasma flow, urinary sodium excretion, hematocrit, plasma renin activity, or concentrations of plasma aldosterone, norepinephrine, or atrial natriuretic factor. CONCLUSIONS: A single large volume paracentesis without albumin replacement causes no disturbances in systemic and renal hemodynamics 48 h after the procedure. These results suggest that a single 5-L paracentesis without albumin infusion is a safe and satisfactory short term option for the management of patients with cirrhosis and tense, diuretic-resistant ascites.

Aged↗
PubMed1997

Cyclins in a dinoflagellate cell cycle.

The dinoflagellates are distinct eukaryotes in having and extranuclear spindle and permanently condensed chromosomes. These cytologic features implicate special adaptations to the molecular mechanisms of cell cycle control. We have demonstrated the presence of cyclin-box-containing polypeptides in dinoflagellates by immunoblotting using peptide-generated antibodies. We identified four major cyclin-box-containing polypeptides. The cell cycle dynamics of these polypeptides were also investigated in synchronized populations, using a newly developed method. Of the four major cyclin-box-containing polypeptides detected, a triplex with apparent molecular weight of 75 kDa did not change appreciably during the cell cycle. For two other cyclin-box-containing polypeptides with apparent molecular weights of 50 and 65 kDa, we observed an early expression in the cell cycle, with the level accumulating and eventually being degraded on the exit of mitosis. At least on cyclin-box-containing polypeptide (50 kDa) was also observed in a protein complex bound to p13suc1 beads. The bound complex head associated histone kinase activity. Variation of this activity corresponded well with the periodic expression of the 50-kDa cyclin-box-containing polypeptide during the cell cycle of Crypthecodinium cohnii. This demonstrates the presence of cyclins and cyclin-dependent kinases in dinoflagellates.

Animals↗
PubMed1997

Effects of insulin on renal function, sympathetic nervous activity and forearm blood flow in normal human subjects.

OBJECTIVE: To assess fully the vasodilatory and sodium-retaining effects of insulin. DESIGN: Prospective physiologic study using a dose-response protocol. SETTING: Clinical investigation unit of a tertiary referral hospital. PARTICIPANTS: Six normal, healthy men. INTERVENTIONS: Subjects were given increasing doses of insulin intravenously from 10 to 1200 mU/m2 per minute, using the euglycemic "clamp" technique. OUTCOME MEASURES: Urinary sodium excretion, systemic and renal hemodynamics, plasma norepinephrine levels and forearm blood flow after each dose. RESULTS: Low doses of insulin (up to 20 mU/m2 per minute) produced a significant antinatriuresis (0.18 [SEM 0.05] v. 0.37 mmol per minute at baseline, p < 0.01) and antidiuresis (2.53 [SEM 0.67] v. 6.21 [SEM 1.66] mL per minute, p < 0.01) with no associated changes in renal hemodynamics or sympathetic nervous activity. Subsequent higher doses of insulin improved urinary volume and sodium excretion to above baseline levels associated with renal and forearm vasodilatation, although mean arterial pressure remained unaltered. CONCLUSIONS: Hyperinsulinemia initially causes an antinatriuresis and antidiuresis through a direct action on the renal tubule. The subsequent phenomenon of escape from renal sodium retention may serve as a regulatory mechanism on sodium homeostasis in conditions associated with hyperinsulinemia and sodium retention.

Adult↗
PubMed1997

A pathologic study of degeneration of the rod and cone populations of the rhodopsin Pro347Leu transgenic pigs.

PURPOSE: Transgenic pigs with rhodopsin (Pro347Leu) mutation exhibited rod-cone degeneration. We compared the pathologic characteristics of the rod degeneration versus those of the cone cells. METHODS: The posterior and peripheral retinas of these transgenic pigs of age 4, 6, 8, 12, 24 and 33 weeks and normal pigs of age 4 and 8 weeks were studied by light and EM and morphometry. RESULTS: The pathologic changes observed in the posterior and peripheral retinas of the transgenic pigs could be conveniently described in 3 phases: I) an initial phase of rapid and extensive degeneration of the rod cells in the first 6 weeks of age; II) an acute phase of cone cell degeneration involving approximately half of the population and lingering rod degeneration in the 6 to 12 weeks of age; and III) a partial cone recovery to be followed by a chronic degenerative phase of the remaining cones cells from 12 to 33 weeks of age. CONCLUSION: Our study showed that the degenerative changes of rod cells could be differentiated from those of the cone cells. Cone and rod populations degenerated along different time schedule with different pathologic features. Hence, treatment for retinitis pigmentosa might vary with the different stages of the disease.

Animals↗